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Abstract: Objectives: Specific potential determinants of infant pain response were assessed in the context of a 4- or 6-month immunization injection. The distal influences of gender, gestational and current age, temperament, and early nociceptive stimuli were considered, as well as the proximal influences of parental and nurse coping-promoting statements within the treatment room. Study design: An observational study design was used. Pain responses in 93 infants receiving an immunization injection were videoed and coded using the Neonatal Facial Coding System (NFCS) and duration of crying was recorded. Parent and nurse vocalizations were coded using the Child–Adult Medical Procedure Interaction Scale-Revised. Results: A multiple regression analysis evaluated the influence of the 5 distal and 2 proximal factors on NFCS scores, and found parental coping-promoting statements in the 30 s period before the injection to have the strongest effect on facial pain response (p <0.01). Parents made significantly more coping-promoting statements (p <0.05), and generally talked more (p <0.05), to female infants than male infants. Conclusions: The findings suggest that parental behavior in the treatment room has a key role in influencing how infants respond to painful procedures. [Copyright &y& Elsevier]